The goal of this application is to establish the Pacific Northwest Regional Center of Excellence (PNWRCE) in NIAID Region X. The two inter-related but distinct PNWRCE themes that we have selected reflect not only the scientific strengths at our institutions but also the unmet needs that we perceive are absent in the NIAID biodefense and emerging disease program. The first theme "Identification of Age-Related Defects in the Immune System to Develop Vaccines and Supplemental Therapies" will include two projects. The overall goal of these projects is to develop new vaccines and immune supplemental therapies for immune vulnerable populations such as aged individuals. The first project a P01 will investigate the hypothesis that certain unifying manipulations can be performed to increase T cell immunity in immune vulnerable populations to a broad group of pathogens. The second project will develop a novel and effective vaccine platform for safely immunizing both healthy and vulnerable populations against YFV. The second theme will center on "The use of systems biology, functional genomics and genetics to characterize pathogen-host response for biodefense and emerging disease organisms." This theme will include four projects with the overall goal of using systems approaches to identify new targets and therapeutics for Category A-C agents. The goal of the first project a P01 is to use systems approaches to identify common host susceptibility alleles and signaling circuitry that enhance highly pathogenic pneumonic viruses and Ebola virus replication and pathogenesis and to identify key cellular targets and immune correlates that influence severe disease outcomes. The goal of the second project a P01 is focused on defining innate immune mechanisms, therapeutic targets, and antiviral compounds that limit flavivirus infection and pathogenesis. The third project an R01 will use systems approaches to characterize Francisella mutants that exhibit either altered intracellular growth rates or induce cellular apoptosis. The last project an RO1 will use a combination of genetic, biochemical, and computational approaches to elucidate B. pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. STRATEGIC MANAGEMENT PLAN/CORE A: Strategic Plan and Management (Project SMP Leader, J. Nelson) STRATEGIC MANAGEMENT PLAN/CORE A DESCRIPTION (provided by applicant): The PNWRCE is a Regional Center of Excellence (RCE) that includes the majority of the institutions in the Northwest including Oregon Health and Science University (OHSU), the University of Washington (UW), Pacific Northwest National Laboratory (PNNL), and the University of Idaho (Ul) as well as institutions outside our region such as the University of Arizona (UA), University of Wisconsin, the University of North Carolina at Chapel Hill, Washington University in St. Louis, the Memorial Sloan-Kettering Cancer Center in New York, and the Rocky Mountain Laboratories (NIAID) in Hamilton, Montana. The Center has a strong multidisciplinary character, exemplified by highly interactive Research Projects and associated Scientific Cores as well as Developmental Projects, Training Programs, and an Emergency Preparedness Program. A strong administrative and organizational structure is vital to the Center's ability to successfully carry out each of the functions of the center to promote synergy between programmatic elements. In this Core, we outline in detail our administrative structure, the role of the Director, Co-Director, Administrator, and Advisory Boards in managing Center activities. Clearly, the success of the Administrative Core is dependent upon its personnel, and we have assembled an experienced team of Directors and Administrators. We are also fortunate to have a Steering Committee and participants that are composed of highly regarded experts in the fields of virology, bacteriology and immunology, as well as proteomics and bioinformatics to provide guidance, selection of projects and career development awards to maintain the function, productivity, flexibility and excellence of the center. The Specific Aims of the Administrative Core are to: 1) Provide an organizational and programmatic structure to promote scientific interactions, research productivity, and training. 2) Provide oversight, planning, priority setting, and decision-making processes. 3) Ensure that the Center is compliant with IRB and IACUC issues. In addition the Administrative Core is tasked with ensuring that the Center continues to meet all criteria described in the NIAID Research Centers of Excellence in Biodefense and Emerging Disease Program and Review Guidelines, including a data sharing plan, state-of-the-art facilities, innovation, multidisciplinary involvement, thematic integration, and synergy among RCEs.